title: A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell responses in humans despite preexisting anti-adenovirus immunity.
abstract: There is an urgent need to develop new tuberculosis (TB) vaccines to safely and effectively boost Bacille Calmette-Guérin (BCG)-triggered T cell immunity in humans. AdHu5Ag85A is a recombinant human type 5 adenovirus (AdHu5)-based TB vaccine with demonstrated efficacy in a number of animal species, yet it remains to be translated to human applications. In this phase 1 study, we evaluated the safety and immunogenicity of AdHu5Ag85A in both BCG-naïve and previously BCG-immunized healthy adults. Intramuscular immunization of AdHu5Ag85A was safe and well tolerated in both trial volunteer groups. Moreover, although AdHu5Ag85A was immunogenic in both trial volunteer groups, it much more potently boosted polyfunctional CD4(+) and CD8(+) T cell immunity in previously BCG-vaccinated volunteers. Furthermore, despite prevalent preexisting anti-AdHu5 humoral immunity in most of the trial volunteers, we found little evidence that such preexisting anti-AdHu5 immunity significantly dampened the potency of AdHu5Ag85A vaccine. This study supports further clinical investigations of the AdHu5Ag85A vaccine for human applications. It also suggests that the widely perceived negative effect of preexisting anti-AdHu5 immunity may not be universally applied to all AdHu5-based vaccines against different types of human pathogens.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: Fiona
authors.initials: F
authors.lastname: Smaill
authors.forename: Mangalakumari
authors.initials: M
authors.lastname: Jeyanathan
authors.forename: Marek
authors.initials: M
authors.lastname: Smieja
authors.forename: Maria Fe
authors.initials: MF
authors.lastname: Medina
authors.forename: Niroshan
authors.initials: N
authors.lastname: Thanthrige-Don
authors.forename: Anna
authors.initials: A
authors.lastname: Zganiacz
authors.forename: Cindy
authors.initials: C
authors.lastname: Yin
authors.forename: Armando
authors.initials: A
authors.lastname: Heriazon
authors.forename: Daniela
authors.initials: D
authors.lastname: Damjanovic
authors.forename: Laura
authors.initials: L
authors.lastname: Puri
authors.forename: Jemila
authors.initials: J
authors.lastname: Hamid
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.forename: Ronan
authors.initials: R
authors.lastname: Foley
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bramson
authors.forename: Jack
authors.initials: J
authors.lastname: Gauldie
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000260:Adenoviruses, Human / Q000276:immunology*; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D032581:Tuberculosis Vaccines / Q000009:adverse effects / Q000276:immunology*; D014611:Vaccination / Q000009:adverse effects; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma